Abstract End stage renal disease (ESRD) requiring maintenance dialysis affects >400,000 Americans and the number of affected adults is projected to exponentially increase in the coming decades. ESRD is associated with various endocrine and metabolic abnormalities, body composition changes, uremic symptoms, lower quality of life and functional status, and higher cardiovascular and mortality risk. However, the degree to which changes in dialysis frequency and dose can alter these adverse outcomes are not known. The NIDDK-sponsored Frequent Hemodialysis Network (FHN) Study is a randomized trial to evaluate whether frequent (6 times per week) vs. conventional (3 times per week) hemodialysis over a 12- month period leads to clinically relevant differences in cardiovascular structure and function, health-related quality of life, physical function, body composition, cognitive function, mental health, nutritional status, hypertension, hyperphosphatemia, and other outcomes. We propose to complement the FHN with additional measurements of targeted endocrine and metabolic factors at baseline and during follow-up to determine if the endocrinopathies associated with ESRD are associated with adverse outcomes; if frequency of dialysis improves these endocrinopathies; and if changes in endocrine function are associated with changes in clinical outcomes. The proposed study will yield novel insights into the endocrine and metabolic abnormalities associated with ESRD and their relation to relevant clinical and patient-centered outcomes. Our three Specific Aims are: Among up to 250 persons with ESRD on maintenance hemodialysis enrolled into the FHN Study: Aim 1: To characterize the prevalence and correlates of abnormalities in pituitary and thyroid- related hormones and mineral metabolism and their association with quality of life, physical and cognitive function, body composition and cardiovascular measures in patients with ESRD. Aim 2: To evaluate the effect of frequent vs. conventional hemodialysis on 12-month changes in endocrine function and whether these changes contribute to differential health-related outcomes. Aim 3: To evaluate the effect of frequent vs. conventional hemodialysis on 12-month changes in targeted hormones and factors related to mineral metabolism and inflammation, and whether these changes are associated with differences in left ventricular hypertrophy. PUBLIC HEALTH RELEVANCE: Project Narrative This is a proposed ancillary study to the Frequent Hemodialysis Network Trial of Daily vs. Conventional Hemodialysis. The major goals of this study are to characterize the endocrinopathies associated with ESRD, their change with dialysis frequency, and the relationship of these changes with health-related outcomes.